Human Epidermal Growth Factor Receptors 1 and 2 (EGFR/HER1 and HER-2/NEU) status in invasive apocrine carcinoma of the breast

The study was undertaken to investigate EGFR and HER-2/neu expression in a cohort of apocrine carcinomas of the breast with emphasis on the classification of the breast carcinomas with apocrine morphology. In total, 55 breast carcinomas morphologically diagnosed as apocrine were evaluated for steroid receptor expression profile characteristic of normal apocrine epithelium (ER-/PR-/AR+), and for the expression of EGFR and Her-2/neu proteins, and the copy number ratios of the genes EGFR/CEP7 and HER-2/CEP17. Another cohort composed of 72 invasive ductal carcinomas of no-special-type was used to further determine the impact of CEP17 polysomy on the interpretation of HER-2/neu testing. Our study confirms that apocrine carcinomas of the breast are molecularly diverse group of carcinomas. Strictly defined, pure apocrine carcinomas (ER-, PR-, AR+) (38 cases, 69%) are either HER-2 overexpressing breast carcinomas (52%) or triple-negative breast carcinomas (48%). Apocrine-like carcinomas (ER+/-, PR+/-, AR+/-) (17 cases, 31%) belong predominantly to the luminal phenotype (76%). Pure apocrine carcinomas show consistent over-expression of either EGFR or Her-2/neu. EGFR gene amplification was observed in two pure apocrine carcinomas and one apocrine-like carcinoma. CEP7 polysomy (defined as three or more CEP7 signals) was seen in 61% pure apocrine carcinomas and 27% of apocrine-like carcinomas and showed a weak positive correlation with EGFR protein expression. HER-2/neu gene amplification is the primary mechanism of Her-2/neu activation and is found in 52% of all apocrine carcinomas. CEP17 polysomy (defined as three or more CEP17 signals) was observed in 10 pure apocrine carcinomas (32%) and 8 apocrine-like carcinomas (50%). CEP17 polysomy may be seen without HER-2/neu gene amplification. Further exploration on a cohort of invasive ductal carcinomas of no-special-type confirmed that increased CEP17 signals may lead to discordant interpretation of HER-2/neu gene amplification in a significant proportion of the cases, depending on which criterion (ratio versus absolute number) is used for interpretation. However, increased gene dosage (>6 HER-2/neu genes or HER-2/CEP17 ratio>2.2), regardless of the evaluation method, is positively correlated with Her-2/neu protein expression.